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[P2–220]: GENETIC FINDINGS USING ADNI MULTIMODAL QUANTITATIVE PHENOTYPES: A 2016 UPDATE
Author(s) -
Yao Xiaohui,
Yan Jingwen,
Nho Kwangsik,
Risacher Shan L.,
Börner Katy,
Saykin Andrew J.,
Shen Li
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.872
Subject(s) - genome wide association study , neuroimaging , phenotype , computational biology , biology , alzheimer's disease neuroimaging initiative , gene , genetics , neuroscience , genotype , single nucleotide polymorphism , cognition , cognitive impairment
Background:White matter hyperintensities (WMH) presumed to represent cerebral small vessel disease, and increased peripheral inflammatory markers, are commonly found in Alzheimer’s disease (AD) but their interrelationships, and their impact on cognitive decline, remains to be fully understood. Methods: Cross-sectional cohort study (n1⁄450), including AD (n1⁄412) and non-AD (n1⁄438) participants, including strata of extensive (n1⁄431) or minimal (n1⁄419) WMH. We identify WMH using multimodal MRI, quantify microstructural integrity as fractional anisotropy (FA) using diffusion tensor imaging, assay serum cytokines using a mutliplex magnetic bead assay, and assess cognitive performance using a standardized battery (including Z-scores from the California Verbal Learning Test, 2nd Ed. for long delayed free recall, and from the Trail Making Test B for executive function). We assess indirect effects using a path model with an inferential bootstrapping procedure (10,000 permutations). Results:We identified a serum inflammatory signature composed of 5 cytokines (tumor necrosis factor, interleukin[IL]-1beta, IL-23, IL-21 and IL-10) that was associated with lower FA within periventricular WMH in AD participants (r 1⁄4 0.713, p 1⁄4 .009) but not in non-AD participants (r 1⁄4 0.218, p 1⁄4 .188). We report an indirect effect of FA within periventricular WMH on executive function that is mediated by the serum inflammatory signature and moderated by AD (index of moderated mediation 8.45, 95% bootstrap confidence interval [2.24, 18.34]). The same moderated mediation effect was not significant for long delayed free recall (6.95, 95% bootstrap confidence interval [-5.03, 22.50]). Conclusions: Microstructural damage within the white matter affected by cerebral small vessel disease affects executive function. This effect is mediated by inflammatory activity specifically in patients with AD.